New screening tool looks for common warning signs.

Katherine McDonell, M.D., a neurologist at the Center of Excellence for Huntington’s disease (HD) at Vanderbilt University Medical Center, has seen many HD patients run afoul of the law.

“We get calls from jail, from the back of a police car, from a patient’s relative in the middle of the night, and it is almost always a young HD patient who has made some really bad decisions and gotten into trouble,” McDonell said.

McDonell’s own experience along with a stream of clinical anecdotes from colleagues inspired her to investigate the frequency of these events and how risky behaviors may predate the early neurological symptoms of HD. McDonell will report her findings in a forthcoming study conducted with principal investigator Daniel Claassen, M.D., division chief of behavioral and cognitive neurology at Vanderbilt.

Illegal Activities and HD

The researchers reviewed the EHRs of 289 patients who had a genetic diagnosis of HD between 2006 and 2020, and found 11 percent had a history of illegal behavior. The average age at which these behaviors occur is 37.

“Not surprisingly, we found that psychiatric dysfunction as a whole was much more common in these patients that have committed unlawful behaviors,” McDonell said. “The extent of this was dramatic. Comorbid psychiatric symptoms were reported in 100 percent of patients with a criminal offense, as well as 80 percent of non-offenders. Rates of depression, irritability, aggression, apathy, perseveration, and delusions were significantly higher in patients with a history of illegal behaviors.”

To explore seeds of the illegal behaviors, the researchers are developing an HD-specific questionnaire to improve recognition of risky behaviors. A preliminary assessment of the tool with 60 HD patients and their caregivers found 80 percent of patients and 91 percent of caregivers reported that the patient had exhibited at least one dangerous behavior. Impulsive/compulsive behaviors and reckless driving were among the top reported, with hypersexuality, verbal and physical altercations, and substance abuse also commonly reported. All these behaviors were more prevalent in young men than women (92 vs. 71 percent) and negatively correlated with age.

“Psychiatric dysfunction as a whole was much more common in these patients that have committed unlawful behaviors; the extent of this was dramatic.”

Tangled Roots of Risky Behaviors

It is hard to separate an individual’s HD from their often traumatic family history, McDonell says. A young person with HD has at least one parent with HD, and they have often experienced the trauma of seeing other family members go through the illness. Growing up witnessing others’ unpredictable behaviors, with grief, and with fear about their own HD status can all contribute to mental illness and impaired judgment.

“There is a ton of psychopathology, a ton of stress that goes along with just growing up in an HD family, whether you have HD or not,” she said.

While social factors can obscure the etiology of risky behaviors, McDonell hypothesizes that their high prevalence may be tied to how HD affects the frontostriatal and mesolimbic networks related to executive function and reward responsivity early on in the disease.

Preempting Punishment

Whatever the genetic and environmental mix, McDonell is focused on getting patients with HD or at risk for the disease treated early. “Some combination of counseling, providing resources, addressing family and social stressors, and prescribing appropriate medications are effective in helping many of our patients,” McDonell said. “But the first step is recognizing these behaviors before they lead to bad consequences, which is what we’re trying to do with the new questionnaire.”

Jeffrey Stovall, M.D., a professor of psychiatry and behavioral sciences medicine at Vanderbilt, works with patients referred from the HD center. He says that the combination of family shame, lack of public awareness about HD, and disjointed health care delivery all contribute to improper or late diagnoses of HD – and sadly, to police apprehension outside the context of the disease.

About the Expert

Katherine E. McDonell, M.D.

Katherine E. McDonell, M.D., is an assistant professor of neurology at Vanderbilt University Medical Center. She specializes in neurodegenerative disorders, is a core faculty member of the Level 1 Center of Excellence for Huntington’s disease at Vanderbilt, and directs Vanderbilt’s predictive genetic testing program for Huntington’s disease.

Jeffrey Stovall, M.D.

Jeffrey Stovall, M.D., is a professor of psychiatry and behavioral sciences medicine and part of the Psychotic Disorders Program at Vanderbilt University Medical Center. His research interests include the development and outcomes of community-based systems of care for individuals with severe mental illness and schizophrenia.